This study was performed to demonstrate an experimental procedure of pulmonary edema induced by angiotensin I (AT I) in rats and to elucidate the mechanism of hemodynamic pulmonary edema. In the previous pilot study, 20 microg/kg of AT I was found to be an adequate dose for inducing pulmonary edema. To elucidate the mechanism of AT I pulmonary edema and protective measures against it, we observed the effects of captopril (CAP, 5 and 10 mg/kg), an angiotensin converting enzyme inhibitor; losartan (LOS, 10 mg/kg), an angiotensin II (AT II)-receptor antagonist; and phentolamine (PHE, 10 mg/kg), an alpha-adrenergic receptor blocker, on AT I-induced pulmonary edema in rats. Similarly, we also observed the effects of CAP (10 and 20 mg/kg) on pulmonary edema induced by 25 microg/kg of adrenaline (ADR) in rats. The development of AT I-induced pulmonary edema was significantly suppressed by CAP and LOS, but was unaffected by PHE. In contrast, the development of ADR-induced pulmonary edema was not suppressed by CAP. These results suggest that AT I-induced pulmonary edema is developed via the AT II and a specific AT II-receptor, without the indirect action of adrenaline.
ABSTRACT-Weperformed this study to demonstrate the experimental procedure for inducing pulmonary edema by angiotensin II (AT II) in rats and to determine the mechanism of hemodynamic pulmonary edema. In the pilot study, 10 pg/ml of AT II was found to be adequate as the edematogenic dose for inducing pulmonary edema. The edematogenic dose of AT II was intravenously given to rats pretreated with 20 mg/kg of an AT II-receptor antagonist, E 4177 (3-[(2"-carboxybiphenyl-4-yl)methyl]-2-cyclopropyl-7-methyl-3H-imidazo [4,5-b]pyridine), and to rats given 10 mg/kg of an alpha-adrenergic blocker, phentolamine. Similarly, pulmonary edema was induced by 25 tcg/ml of adrenaline in rats pretreated with E 4177 (20 mg/kg) and rats with no pretreatment. E 4177 completely suppressed the development of AT II-induced pulmonary edema, whereas phentolamine could not. On the contrary, E 4177 could not suppress the development of adrenaline-induced pulmonary edema. We concluded that AT II-induced pulmonary edema will develop via the specific AT II receptor without the indirect action of adrenaline.Keywords: Pulmonary edema, Angiotensin II, Adrenaline, Angiotensin II-receptor antagonist, PhentolamineHeart failure causes an increase in systemic vascular resistance and an accumulation of excess fluid as the compensatory adaptations of enhanced activities of the sympathetic nervous system and the renin-angiotensin system. The clinical features relating to pulmonary edema arise in the end-stage of the left ventricular failure due to the excessive compensatory adaptations.Angiotensinconverting enzyme inhibitors have currently attracted the attention of physicians as effective drugs that improve the prognostic outcomes of patients with heart failure (1). Since the drugs suppress the production of angiotensin II (AT II) which has a vigorously vasoconstrictive effect, they bring about a favorable clinical course in those patients. Although many studies have established experimentally that high doses of adrenaline, one of the most powerful cardiac stimulants, induce pulmonary edema as the result of increased afterload in systemic circulation which elevates the left atrial pressure (2), there are no reports to our knowledge, on the experimental induction of pulmonary edema by AT II. In the course of the study on pulmonary edema, we had been concerned with the vasoconstrictive effect of AT II and found that the bolus intravenous injection of AT II also induced pulmonary edema in rats. We therefore undertook the present study for the following reasons: 1) to propose the experimental procedure for inducing pulmonary edema by the administration of AT II in rats and 2) to determine the mechanism of AT II-induced pulmonary edema and the protective measures against it. MATERIALS AND METHODS Animals and outline of the experimentMale albino rats of the Wistar strain (n=57) weighing 250-300 g were purchased from Saitama Animal Lab.(Saitama) and housed under controlled conditions for at least two weeks before the experiments. They were randomly divided into...
To develop a new method for accurately predicting creatinine clearance (Ccr) in the debilitated elderly without urine collections, the total muscle volume of both thighs (MV thigh), as a new predictive parameter, was calculated using computed tomography in 68 debilitated patients aged 61–92 years. A regression line between 24-hour urinary creatinine excretion and MV thigh was divided by serum creatinine (Scr), and then the following formula was derived: Ccr(ml/min) = 9 × [MV thigh (cm3) –– 100]/[1,000 × Scr(mg/dl)] Predicted Ccr by the new method more closely correlated with measured Ccr (r = 0.862) than did predicted Ccr by Cockcroft and Gault’s method (the C-G method) (r = 0.727). Statistical analysis of prediction error (= predicted Ccr-measured Ccr) suggested that the new method could provide more accurate and less biased estimations of Ccr than did the C-G method, even in patients with renal insufficiency. By using computed tomography, we have proposed a more accurate method for predicting Ccr of the debilitated elderly than the C-G method, although the new method has inherent disadvantages of radiation exposure and high cost.
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